Understanding and Managing Ultra High-Risk Chronic Lymphocytic Leukemia
Understanding and Managing Ultra High-Risk Chronic Lymphocytic Leukemia
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DOI：
10.1182/asheducation-2010.1.481
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发表时间：
2010-12-01
影响因子：
3
通讯作者：
Zenz, Thorsten
中科院分区：
文献类型：
--
作者：
Stilgenbauer, Stephan;Zenz, Thorsten
现代治疗方法如化学免疫疗法（例如，氟达拉滨/环磷酰胺/利妥昔单抗或FCR）在大多数慢性淋巴细胞白血病（CLL）患者中是高度有效的。然而，仍然有一个小的，但具有挑战性的亚组的患者显示超高风险遗传学（17 p缺失，TP 53突变）和/或化疗免疫反应差。这些患者的中位预期寿命在标准方案下低于2至3年。因此，具有17 p缺失（并且可能还具有唯一的TP 53突变）的CLL应该用替代策略治疗。虽然p53缺陷似乎在我们对这一超高风险组的理解中起着核心作用，但根据现有的预后模型，至少有一半的病例是不可预测的。目前用于p53缺陷或对化学免疫疗法反应差的患者的治疗方法应依赖于独立于p53起作用的药物，如阿仑单抗、来那度胺、flavopiridol和目前临床试验中可用的越来越多的新型化合物（或其组合）。超高风险CLL患者的生存时间不佳表明，应在临床试验中为符合条件的患者提供降低强度的异基因干细胞移植或实验方法的巩固治疗。
Modern treatment approaches such as chemoimmunotherapy (e.g., fludarabine/cyclophosphamide/rituximab or FCR) are highly effective in the majority of chronic lymphocytic leukemia (CLL) patients. However, there remains a small but challenging subgroup of patients who show ultra high-risk genetics (17p deletion, TP53 mutation) and/or poor response to chemoimmunotherapy. The median life expectancy of these patients is below 2 to 3 years with standard regimens. Accordingly, CLL with the 17p deletion (and likely also with sole TP53 mutation) should be treated with alternative strategies. While p53 defects appear to play a central role in our understanding of this ultra high-risk group, at least half of the cases will not be predictable based on existing prognostic models. Current treatment approaches for patients with p53 defects or poor response to chemoimmunotherapy should rely on agents acting independently of p53, such as alemtuzumab, lenalidomide, flavopiridol, and a growing number of novel compounds (or combinations thereof) currently available in clinical trials. Poor survival times of patients with ultra high-risk CLL suggest that eligible patients should be offered consolidation with reduced-intensity allogeneic stem-cell transplantation or experimental approaches in clinical trials.